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Selected causes of unilateral or bilateral gynecomastia in children and adolescents

Selected causes of unilateral or bilateral gynecomastia in children and adolescents
  Associated clinical features
Physiologic causes
Neonatal
  • May be associated with galactorrhea; usually resolves spontaneously within the first year of life
Pubertal
  • Occurs at mid-puberty: during peak height velocity at age 12 to 14 years; pubic hair SMR stage 3 to 4; testicular volume 8 to 10 mL
Pathologic causes
Drugs
Exogenous estrogen
  • Source of exogenous estrogen (eg, combined oral contraceptive pills, topical estrogen cream)
Other drugs
  • History of exposure to drug or other substances associated with gynecomastia (refer to UpToDate content on drugs that cause gynecomastia)
Hypogonadism
Primary (hypergonadotropic)
  • Klinefelter syndrome
  • Tall, thin body habitus; small firm testes in pubertal-aged males
  • Cryptorchidism
  • One or both testes not within the scrotum (or history of testis that is not within the scrotum)
  • Defect in testosterone synthesis (eg, 17-ketosteroid reductase deficiency)
  • Atypical genitalia; undervirilization
  • Acquired primary hypogonadism
  • History of testicular insult or injury (eg, surgery, radiation, systemic illness, etc)
Secondary (hypogonadotropic)
  • Acquired secondary hypogonadism
  • Insult to hypothalamic-pituitary axis (eg, surgery, radiation, trauma, etc)
  • Hyperprolactinemia
  • Galactorrhea
Tumors
Testicular cancer (Leydig or Sertoli cell)
  • Testicular mass; increased risk with history of cryptorchidism (any testicular cancer); increased risk in Peutz-Jeghers syndrome (Sertoli cell tumors)
Feminizing adrenal tumor
  • Abdominal mass
Lactotroph adenoma (prolactinoma)
  • Galactorrhea, hypogonadism, vision problems, headaches
hCG-producing tumors
  • Testicular (germ cell)
  • Testicular mass; increased risk with history of cryptorchidism
  • Extragonadal germ cell tumor (eg, mediastinal, retroperitoneal, intracranial)
  • May be detected with chest or abdominal imaging
  • Nontrophoblastic hCG-producing tumor
  • May be detected with imaging (chest, abdomen, brain)
Other causes
Chronic liver or kidney disease/malnutrition
  • Underweight; findings associated with chronic liver or kidney disease (eg, hepatomegaly, edema, etc)
Hyperthyroidism
  • Goiter, accelerated growth, weight loss, ophthalmopathy, tachycardia, increased appetite, tremor
Aromatase excess syndrome
  • Accelerated early linear growth, prepubertal gynecomastia, testicular failure
Androgen resistance (eg, partial androgen insensitivity)
  • Atypical genitalia; undervirilization; muscle fasciculations, weakness, and calf hypertrophy (X-linked spinal and bulbar muscular atrophy)
Congenital adrenal hyperplasia
  • 11-beta-hydroxylase deficiency
  • Premature adrenarche, early puberty, accelerated linear growth, hypertension
  • 3-beta-hydroxysteroid dehydrogenase deficiency
  • Atypical genitalia, undervirilization
  • Late-onset 21-hydroxylase deficiency
  • Premature adrenarche with advanced bone age, accelerated linear growth during childhood, acne
Ovotesticular disorder of sex development (previously "true hermaphroditism")
  • Atypical genitalia (presence of both ovarian follicular and testicular tubular tissue in a single individual); undervirilization
SMR: sexual maturity rating (Tanner stage); hCG: human chorionic gonadotropin.
References:
  1. Braunstein GD. Gynecomastia. N Engl J Med 1993; 328:490.
  2. Braunstein GD. Clinical practice. Gynecomastia. N Engl J Med 2007; 357:1229.
  3. Ma NS, Geffner ME. Gynecomastia in prepubertal and pubertal men. Curr Opin Pediatr 2008; 20:465.
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